Definitive conclusions will be sought to the still unsettled questions of the significance of hyaluronidase in cancer invasiveness. The enzyme activity will be measured by parallel analyses using the two chief methods - hyaluronate depolymerization and N-acetyglucosamine liberation - to determine whether contradictory reports may have resulted from differences in analytical approach. The enzyme activities both of highly and of poorly invasive cancer cells and tissues and of benign and normal controls will be compared to determine if activity can be related to invasiveness. Human autopsy and surgical biopsy specimens will be used, as will mouse and tissue culture material. The tissue hyaluronidase activity will be measured in relation to fetal and neonatal development of the rat for possible correlations with the known enhancement of cancer cell transplantability by fetal tissue and with the known greater susceptibility of the fetus and neonate to carcinogens. We will determine if fetal antigens can act as in vitro inhibitors of hyaluronidase and if relationships exist between human blood levels of fetal antigens and those of the hyaluronidase inhibitor. The influence on the human and guinea pig serum inhibitor levels of Bacillus Calmette-Guerin (BCG) stimulation of the immune response used in cancer therapy will be studied. Increase in the blood-serum inhibitor level will be considered as a possible defensive response, one that might also reflect the clinical state and possibly serve as an early indicator of cancer.